Inhibition of matrix metalloproteinases attenuates brain damage in experimental meningococcal meningitis.

Ricci, Susanna; Grandgirard, Denis; Wenzel, Michael; Braccini, Tiziana; Salvatore, Paola; Oggioni, Marco R; Leib, Stephen; Koedel, Uwe (2014). Inhibition of matrix metalloproteinases attenuates brain damage in experimental meningococcal meningitis. BMC infectious diseases, 14(726), p. 726. BioMed Central 10.1186/s12879-014-0726-6

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BackgroundApproximately 7% of survivors from meningococcal meningitis (MM) suffer from neurological sequelae due to brain damage in the course of meningitis. The present study focuses on the role of matrix metalloproteinases (MMPs) in a novel mouse model of MM-induced brain damage.MethodsThe model is based on intracisternal infection of BALB/c mice with a serogroup C Neisseria meningitidis strain. Mice were infected with meningococci and randomised for treatment with the MMP inhibitor batimastat (BB-94) or vehicle. Animal survival, brain injury and host-response biomarkers were assessed 48 h after meningococcal challenge.ResultsMice that received BB-94 presented significantly diminished MMP-9 levels (p¿<¿0.01), intracerebral bleeding (p¿<¿0.01), and blood-brain barrier (BBB) breakdown (p¿<¿0.05) in comparison with untreated animals. In mice suffering from MM, the amount of MMP-9 measured by zymography significantly correlated with both intracerebral haemorrhage (p¿<¿0.01) and BBB disruption (p¿<¿0.05).ConclusionsMMPs significantly contribute to brain damage associated with experimental MM. Inhibition of MMPs reduces intracranial complications in mice suffering from MM, representing a potential adjuvant strategy in MM post-infection sequelae.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Grandgirard, Denis and Leib, Stephen

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1471-2334

Publisher:

BioMed Central

Language:

English

Submitter:

Stephen Leib

Date Deposited:

06 Feb 2015 16:29

Last Modified:

28 Nov 2020 02:25

Publisher DOI:

10.1186/s12879-014-0726-6

PubMed ID:

25551808

BORIS DOI:

10.7892/boris.61929

URI:

https://boris.unibe.ch/id/eprint/61929

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